People with schizophrenia have significant challenges functioning in society, including finding and maintaining employment, making friends, and living independently. These challenges place a tremendous burden on people with schizophrenia, as well as their families and caregivers, and are the primary source of the very high cost of medical care for this severe mental illness. It had been assumed for a long time that these challenges in functional abilities were caused by the overt symptoms of schizophrenia, like hallucinations and delusions;however research has now shown that these challenges are largely a result of problems with cognitive abilities, like attention and memory. For example, a person with schizophrenia with relatively good cognitive function is more likely to be able hold down a job even with significant hallucinations and delusions;while a person with relatively poor cognitive function is very unlikely to do so even if they have fewer hallucinations and delusions. This has sparked a tremendous amount of research into how to improve cognitive function in people with schizophrenia, because improving cognitive function should improve overall quality of life and reduce overall health care costs. While most of this research has focused on discovering and testing new drugs that might improve cognitive function, we are taking a radically different and innovative approach. We are harnessing discoveries in basic brain science that have shown how to build computerized training programs that directly re-wire how the brain processes information, and as a result, improve cognitive function. This basic research is now ready to move out of the lab and into the real world to help people with schizophrenia. We have already developed a prototype version of such a program, and independent scientists have shown that it improves cognitive function in people with schizophrenia. However, the prototype is not a final product, and we cannot make it available until we do a study with the Food and Drug Administration (FDA). This grant will allow us to develop the prototype into a final product, and conduct a "gold-standard" clinical trial with leading independent academic scientists and the FDA to show that it works. Our first goal is to adapt the prototype into a single, secure, web-based application that will allow people with schizophrenia to use the program from any computer, including those at community mental health centers. We will also build a web-based system that lets doctors securely keep track of how their patients are doing with the program. Our second goal is to conduct a clinical trial comparing the new program to standard computer games to demonstrate that this science is significantly better than what is available now. At the end of this grant, we will be ready to make the new program available as a doctor's prescription for people with schizophrenia. Over time, this fundamental technology will be adapted to address many neurological and psychiatric illnesses. We hope that this scientific advance can form the basis for a real improvement in the lives of millions of people, and in the lives of their family members and caregivers. PUBLIC HEALTH RELEVANCE: People with schizophrenia have significant problems with thinking (like attention and memory) that make it difficult for them to hold down jobs, make friends, and live independently. We plan to build and test a new kind of computerized training program that helps improve think abilities in people with schizophrenia by improving the way their brains work. This will help people with schizophrenia become more integrated with society and able to achieve their goals in life, while reducing the overall societal cost of caring for this severe mental illness.